Which Tumor Suppressor Gene Plays an Important Role in Oncogenesis of Oral Cancer?

口腔領域癌の遺伝子学的解析はあまり行われていないため, 本稿では当科における癌抑制遺伝子異常の検索結果を用いて, 口腔癌においてどの遺伝子が重要な役割を果たしているのかを検討した。試料は, 口腔扁平上皮癌組織と, 同一症例の正常組織を用いた。RB遺伝子とWT遺伝子についてはサザンブロッティング法により, また, APC, P53, VHL, p15, p16, p18遺伝子についてはPCR-SSCP法および塩基配列決定法を用いて検索した。さらに, APC遺伝子についてはエクソン11のポリモルフィズムを利用したPCR-LOH分析をあわせて行った。以下に示す結果を得た。(1)APC遺伝子の点突然変異は8.3%, APC-LOHは informative 症例中の72.7%に認められた。(2)p16遺伝子とp18遺伝子の点突然変異はそれぞれ4.0%, 3.8%に認められた。p15遺伝子異常は認められなかった。(3)p53心遺伝子異常は7.7%に認められた。(4)WT遺伝子の部分欠失を6.5%に認めた。(5)RB遺伝子とVHL遺伝子の異常は認められなかった。以上の結果から, 種々の癌抑制遺伝子のうち, 特にAPC遺伝子が口腔扁平上皮癌発生に重要な役割を果たしていることが示唆された。Since there are few molecular biological studies on oral cancer, we evaluated genes which would play an important role in the oncogenesis of oral cancer based on our previous studies. To elucidate whether or not abnormalities of RB and WT genes could contribute to the development of oral squamous-cell carcinoma (SCC), genomic DNAs obtained from tumors and corresponding normal tissues were examined with Southern blotting. On the other hand, PCR-SSCP (polymerase chain reaction single-strand conformation polymorphism) and sequence analyses were performed to detect possible mutations of APC, VHL, p15, p16, p18 and p53. We also examined the tissue samples to detect loss of heterozygosity (LOH) at exon 11 of APC gene by PCR-LOH assay. We obtained the following results: (1) Point mutations of APC gene in tumor tissues were identified in 8.3(nil)atients with oral SCC, and PCR-LOH assay revealed LOH at exon 11 of APC gene in 72.71024720030f informative cases. (2) Point mutations of p16 and p18 genes were detected in 4.0-0x1.db55b085084p-148nd 3.80f oral SCC patients, respectively. However, no mutation of p15 gene was found. (3) Abnormalities of p53 gene were detected in 7.726725462457f all cases. (4) Southern blotting revealed partial deletions and rearrangements of WT gene in 6.50f the cases. (5) No abnormality of VHL and RB genes was detected in any of the cases. These results suggest that APC gene is most significantly associated with the development of human oral SCC among the known tumor suppressor genes